First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study.

Introduction: The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. Methods and Analysis: This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. Ethics and Dissemination: The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04767438.

Consumption of polyunsaturated fat improves the saturated fatty acid-mediated impairment of HDL antioxidant potential.

SCOPE: The present study aimed to compare the effects of diets containing high-fat, high-cholesterol and saturated fatty acids (HFHC-SFA) and HFHC-polyunsaturated fatty acids-containing (HFHC-PUFA) diets on two major antiatherogenic functions of HDL, the HDL antioxidant function and the macrophage-to-feces reverse cholesterol transport. METHODS AND RESULTS: Experiments were carried out in mice fed a low-fat, low-cholesterol (LFLC) diet, an HFHC-SFA diet or an HFHC-PUFA diet in which SFAs were partly replaced with an alternative high-linoleic and α-linolenic fat source. The HFHC-SFA caused a significant increase in serum HDL cholesterol and phospholipids as well as elevated levels of oxidized HDL and oxidized LDL. Replacing SFA with PUFA significantly reduced the levels of these oxidized lipoproteins and enhanced the ability of HDL to protect LDL from oxidation. The SFA-mediated impairment of HDL antioxidant potential was not associated with the cholesterol content of the diet, obesity or insulin resistance. In contrast, the effect of the HFHC diets on fecal macrophage-derived cholesterol excretion was independent of the fatty acid source. CONCLUSION: SFA intake impairs the antioxidant potential of HDL and increases serum levels of oxidized lipoprotein species whereas the antioxidant potential of HDL is enhanced after PUFA consumption.

Standardized peptidome profiling of human serum for the detection of pancreatic cancer.

OBJECTIVE: To establish new biomarkers for accurate diagnosis of pancreatic cancer (PC) using a standardized serum peptidome profiling and compare the results with those from the tumor marker, CA 19-9. METHODS: Serum samples from 102 patients (55 with chronic pancreatitis and 47 with PC) and 56 healthy controls were collected and analyzed following a protocol that was rigorously designed to prevent preanalytical variation. Serum peptides were extracted using immobilized copper ion chromatography on a robotic platform. Mass spectra were acquired by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry on an Autoflex II spectrometer (Bruker Daltonics, Bremen, Germany). Statistical analysis was performed using the Clinprotools 2.2 software (Bruker Daltonics) and the SPSS 15.0 software (SPSS Inc, Chicago, Ill). RESULTS: Standardized peptidome profiling showed a median coefficient of variation of 11.6% calculated using all the extracted peptides and negligible influence of sex and age on peptidome profiles. The diagnostic sensitivity was 89.9%, and the diagnostic specificity was 92.7%, using 2 serum features and CA 19-9 serum concentration. Healthy controls were differentiated from patients with PC and chronic pancreatitis, with the use of 3 features of the peptidome (diagnostic sensitivity, 98.2%; diagnostic specificity, 97.1%). CONCLUSIONS: Standardized serum peptidome profiling could be a useful tool to improve biochemical diagnosis of PC in combination with the classic tumor marker, CA 19-9.